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Find video protocols related to scientific articles indexed in Pubmed.
Regioselective Metal-free Decarboxylative Multicomponent Coupling of ?-Amino acids, Aldehydes and Isonitriles leading to N-substituted azacyclic-2-carboxamides with Antithrombotic activity.
J. Org. Chem.
PUBLISHED: 11-20-2014
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An atom-economical regioselective synthesis of N-substituted prolinamides or N-substituted pirperidine-2-carboxamides via a metal-free decarboxylative multicomponent coupling between L-proline or pipecolic acid, aldehydes and isonitriles is described. The cascade event involves sequential imine formation, decarboxylation, isonitrile insertion and hydrolysis to afford the product in one-pot. Two of the prolinamides were found to display appreciable antithrombotic activity via inhibition of platelet aggregation.
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Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents.
ACS Med Chem Lett
PUBLISHED: 11-13-2014
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New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 ?M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 ?M·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
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RAD6 promotes homologous recombination repair by activating the autophagy-mediated degradation of heterochromatin protein HP1.
Mol. Cell. Biol.
PUBLISHED: 11-12-2014
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Efficient DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. Unrepaired or mis-repaired DSBs cause chromosomal rearrangements that can result in severe consequences such as tumorigenesis. RAD6 is an E2 ubiquitin-conjugating enzyme that plays a pivotal role in repairing UV-induced DNA damage. Here, we present evidence that RAD6 is also required for DNA DSB repair via homologous recombination (HR) by specifically regulating the degradation of heterochromatin protein 1? (HP1?). Our study indicates that RAD6 physically interacts with HP1? and ubiquitinates HP1? at residue K154, thereby promoting HP1? degradation through the autophagy pathway and eventually leading to an open chromatin structure that facilitates efficient HR DSB repair. Furthermore, bioinformatics studies have indicated that the expression of RAD6 and HP1? exhibits an inverse relationship and correlates with the survival rate of patients.
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Revisiting Einstein's brain in Brain Awareness Week.
Biosci Trends
PUBLISHED: 11-11-2014
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Albert Einstein's brain has long been an object of fascination to both neuroscience specialists and the general public. However, without records of advanced neuro-imaging of his brain, conclusions regarding Einstein's extraordinary cognitive capabilities can only be drawn based on the unique external features of his brain and through comparison of the external features with those of other human brain samples. The recent discovery of 14 previously unpublished photographs of Einstein's brain taken at unconventional angles by Dr. Thomas Stoltz Harvey, the pathologist, ignited a renewed frenzy about clues to explain Einstein's genius. Dr. Dean Falk and her colleagues, in their landmark paper published in Brain (2013; 136:1304-1327), described in such details about the unusual features of Einstein's brain, which shed new light on Einstein's intelligence. In this article, we ask what are the unique structures of his brain? What can we learn from this new information? Can we really explain his extraordinary cognitive capabilities based on these unique brain structures? We conclude that studying the brain of a remarkable person like Albert Einstein indeed provides us a better example to comprehensively appreciate the relationship between brain structures and advanced cognitive functions. However, caution must be exercised so as not to over-interpret his intelligence solely based on the understanding of the surface structures of his brain.
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Amide Groups Switch Selectivity: C-H Trifluoromethylation of ?,?-Unsaturated Amides and Subsequent Asymmetric Transformation.
Org. Lett.
PUBLISHED: 11-10-2014
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The first direct C-H ?-trifluoromethylation of unsubstituted or ?-alkyl-substituted ?,?-unsaturated carbonyl compounds under metal-free conditions was realized with excellent regio- and stereoselectivity as well as a very broad substrate scope. Both olefinic and allylic trifluoromethylation products are accessible with high selectivities by altering the substrate substitutions. The resultant olefinic products, namely (E)-?-trifluoromethyl (CF3) ?,?-unsaturated hydroxamic acid derivatives, served as acceptors in organocatalytic asymmetric Michael addition reactions to give hydroxamic acid derivatives bearing a chiral CF3-substituted stereocenter with high enantioselectivities.
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Genetic Variation in PSCA is Associated with Bladder Cancer Susceptibility in a Korean Population.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population.
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Late onset temperature reduction can retard aging process in aged fish via a combined action of antioxidant system and IIS pathway.
Rejuvenation Res
PUBLISHED: 10-10-2014
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Two different mechanisms are considered to be related with aging. Cumulative molecular damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by insulin and insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway is the second mechanism (IIS concept). Temperature reduction (TR) is known to modulate aging and prolong lifespan in a variety of organisms, but the mechanisms remain poorly defined. Here we first demonstrate that late onset TR from 26oC to 22oC extends mean lifespan and maximum lifespan by approximately 5.2 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We then show that TR is able to decrease the accumulation of histological aging markers senescence-associated ?-galactosidase (SA-?-Gal) in the epithelium and lipofuscin (LF) in the liver, and to reduce the protein oxidation and lipid peroxidation levels in the muscle. We also show that TR can enhance the activities of catalase, glutathione peroxidase and superoxide dismutase, and stimulate the synthesis of SirT1 and FOXO, both of which are the downstream regulator of IIS pathway. Taken together, our findings suggest that late onset TR, a simple non-intrusion intervention, can retard aging process in aged fish, resulting in their lifespan extension, via a synergistic action of antioxidant system and IIS pathway. This also suggests that combined assessment of ROS concept and IIS concept will contribute to providing more comprehensive view of anti-aging process.
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IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo.
Nature
PUBLISHED: 09-30-2014
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TP53 is commonly altered in human cancer, and Tp53 reactivation suppresses tumours in vivo in mice (TP53 and Tp53 are also known as p53). This strategy has proven difficult to implement therapeutically, and here we examine an alternative strategy by manipulating the p53 family members, Tp63 and Tp73 (also known as p63 and p73, respectively). The acidic transactivation-domain-bearing (TA) isoforms of p63 and p73 structurally and functionally resemble p53, whereas the ?N isoforms (lacking the acidic transactivation domain) of p63 and p73 are frequently overexpressed in cancer and act primarily in a dominant-negative fashion against p53, TAp63 and TAp73 to inhibit their tumour-suppressive functions. The p53 family interacts extensively in cellular processes that promote tumour suppression, such as apoptosis and autophagy, thus a clear understanding of this interplay in cancer is needed to treat tumours with alterations in the p53 pathway. Here we show that deletion of the ?N isoforms of p63 or p73 leads to metabolic reprogramming and regression of p53-deficient tumours through upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid peptide co-secreted with insulin by the ? cells of the pancreas. We found that IAPP is causally involved in this tumour regression and that amylin functions through the calcitonin receptor (CalcR) and receptor activity modifying protein 3 (RAMP3) to inhibit glycolysis and induce reactive oxygen species and apoptosis. Pramlintide, a synthetic analogue of amylin that is currently used to treat type 1 and type 2 diabetes, caused rapid tumour regression in p53-deficient thymic lymphomas, representing a novel strategy to target p53-deficient cancers.
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Comparative genomic analysis of transgenic poplar dwarf mutant reveals numerous differentially expressed genes involved in energy flow.
Int J Mol Sci
PUBLISHED: 09-03-2014
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In our previous research, the Tamarix androssowii LEA gene (Tamarix androssowii late embryogenesis abundant protein Mrna, GenBank ID: DQ663481) was transferred into Populus simonii × Populus nigra. Among the eleven transgenic lines, one exhibited a dwarf phenotype compared to the wild type and other transgenic lines, named dwf1. To uncover the mechanisms underlying this phenotype, digital gene expression libraries were produced from dwf1, wild-type, and other normal transgenic lines, XL-5 and XL-6. Gene expression profile analysis indicated that dwf1 had a unique gene expression pattern in comparison to the other two transgenic lines. Finally, a total of 1246 dwf1-unique differentially expressed genes were identified. These genes were further subjected to gene ontology and pathway analysis. Results indicated that photosynthesis and carbohydrate metabolism related genes were significantly affected. In addition, many transcription factors genes were also differentially expressed in dwf1. These various differentially expressed genes may be critical for dwarf mutant formation; thus, the findings presented here might provide insight for our understanding of the mechanisms of tree growth and development.
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[Biomechanical study of the influence of stability for the pedicle screws fixation by injured vertebral screw when the pedicle cortex perforation].
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 09-02-2014
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To explore the impact of pedicle cortex perforation on the stability of internal fixation of the vertebral body fracture,and to compare the stability of the vertebrae with pedicle cortex perforation after the injured vertebra transpedicular screw fixation by different ways.
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Crystal structure of diethyl [(4-nitro-phenyl-amino)(2-hy-droxy-phen-yl)meth-yl]phospho-nate methanol monosolvate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 09-01-2014
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In the title compound, C17H21N2O6P·CH3OH, the planes of the 4-nitro-aniline and 2-hy-droxy-phenyl groups form a dihedral angle of 84.04?(8)°. The P atom exhibits tetra-hedral geometry involving two O-ethyl groups, a C? atom and a double-bonded O atom. In the crystal, O-H?O, N-H?O and C-H?O hydrogen bonds link the ?-amino-phospho-nic acid and methanol mol-ecules into chains that propagate parallel to the a axis.
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Association between Nutrition Label Reading and Nutrient Intake in Korean Adults: Korea National Health and Nutritional Examination Survey, 2007-2009 (KNHANES IV).
Korean J Fam Med
PUBLISHED: 07-25-2014
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Nutrition labels provide various information on the nutrient contents of food. However, despite the recent increase in the interest in dietary intake and expansion of related policies, studies on the association between nutrition label reading and dietary intake are lacking in Korea.
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Thermo-responsive release of curcumin from micelles prepared by self-assembly of amphiphilic P(NIPAAm-co-DMAAm)-b-PLLA-b-P(NIPAAm-co-DMAAm) triblock copolymers.
Int J Pharm
PUBLISHED: 07-24-2014
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Thermo-responsive micelles are prepared by self-assembly of amphiphilic triblock copolymers composed of a poly(l-lactide) (PLLA) central block and two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) lateral blocks, using solvent evaporation/film hydration method. The resulting micelles exhibit very low critical micelle concentration (CMC) which slightly increases from 0.0113 to 0.0144mgmL(-1) while the DMAAm content increases from 31.8 to 39.4% in the hydrophilic P(NIPAAm-co-DMAAm) blocks. The lower critical solution temperatures (LCST) of copolymers varies from 44.7°C to 49.4°C in water as determined by UV spectroscopy, and decreases by ca. 3.5°C in phosphate buffered saline (PBS). Curcumin was encapsulated in the core of micelles. High drug loading up to 20% is obtained with high loading efficiency (>94%). The LCST of drug loaded micelles ranges from 37.5 to 38.0°C with drug loading increasing from 6.0 to 20%. The micelles with diameters ranging from 47.5 to 88.2nm remain stable over one month due to the negative surface charge as determined by zeta potential (-12.4 to -18.7mV). Drug release studies were performed under in vitro conditions at 37°C and 40°C, i.e. below and above the LCST, respectively. Initial burst release is observed in all cases, followed by a slower release. The release rate is higher at 40°C than that at 37°C due to thermo-responsive release across the LCST. On the other hand, micelles with lower drug loading exhibit higher release rate than those with higher drug loading, which is assigned to the solubility effect. Peppas' theory was applied to describe the release behaviors. Moreover, the in vitro cytotoxicity of copolymers was evaluated using MTT assay. The results show that the copolymers present good cytocompatibility. Therefore, the nano-scale size, low CMC, high drug loading and stability, as well as good biocompatibility indicate that these thermo-responsive triblock copolymer micelles present a good potential as carrier for targeted delivery of anticancer drugs.
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Risk factors and incidence for peripheral arterial disease in patients with typical lumbar spinal stenosis.
Korean J Spine
PUBLISHED: 07-03-2014
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Intermittent claudication (IC) is a typical symptom of peripheral arterial disease (PAD) and lumbar spinal stenosis (LSS). In order to prevent misdiagnosis of vascular disease, it is important to know the incidence of and risk factors for PAD in patients with LSS. Therefore, the aim of our study was to evaluate the incidence of and risk factors for PAD in patients with typical and severe LSS who underwent spinal surgical treatment.
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Synthesis of TiO2 nanotubes with ZnO nanoparticles to achieve antibacterial properties and stem cell compatibility.
Nanoscale
PUBLISHED: 06-28-2014
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To endow titanium (Ti) with antibacterial properties, different concentrations of zinc oxide (ZnO) nanoparticles were decorated on anodized titanium dioxide (TiO2) nanotubes by a simple hydrothermal treatment method. The particle sizes of ZnO, which were evenly distributed and tightly adherent to the walls of the Ti nanotubes, ranged from 20-50 nm. Results from this study showed that Zn was released from the TiO2 nanotubes in a constant, slow, and biologically inspired manner. Importantly, the results showed that the ZnO decorated TiO2 nanotubular samples inhibited Streptococcus mutants and Porphyromonas gingivalis growth compared to control unmodified Ti samples. Specifically, S. mutants and P. gingivalis growth were both reduced 45-85% on the ZnO decorated Ti samples compared to Ti controls after 7 days of culture. When examining the mechanism of action, it has been further found for the first time that the ZnO decorated Ti samples inhibited the expression of Streptococcus mutans bacterial adhesion genes. Lastly, the results showed that the same samples which decreased bacterial growth the most (0.015 M precursor Zn(NO3)2 samples) did not inhibit mesenchymal stem cell growth compared to Ti controls for up to 7 days. In summary, results from this study showed that compared to plain TiO2 nanotubes, TiO2 decorated with 0.015 M ZnO provided unprecedented antibacterial properties while maintaining the stem cell proliferation capacity necessary for enhancing the use of Ti in numerous medical applications, particularly in dentistry.
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Functional characterization of Cinnamoyl-CoA Reductase (CCR) in birch (Betula platyphylla × Betula pendula) through overexpression and suppression analysis.
Physiol Plant
PUBLISHED: 06-20-2014
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We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and first internode of Betula platyphylla and characterized its functions in lignin biosynthesis, wood formation, and tree growth through transgenic approaches. We generated overexpression and suppression transgenic lines and analyzed them in comparison with the wild-type in terms of lignin content, anatomical characteristics, height and biomass. We found that BpCCR1 overexpression could increase lignin content up to 14.6%, and its underexpression decreased lignin content by 6.3%. Surprisingly, modification of BpCCR1 expression led to conspicuous changes in wood characteristics, including xylem vessel number and arrangement, and secondary wall thickness. The growth of transgenic trees in terms of height was also significantly influenced by the modification of BpCCR1 genes. We discussed the functions of BpCCR1 in the context of a phylogenetic tree built with CCR genes from multiple species.
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Analysis of the leaf methylomes of parents and their hybrids provides new insight into hybrid vigor in Populus deltoides.
BMC Genet.
PUBLISHED: 06-20-2014
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Plants with heterosis/hybrid vigor perform better than their parents in many traits. However, the biological mechanisms underlying heterosis remain unclear. To investigate the significance of DNA methylation to heterosis, a comprehensive analysis of whole-genome DNA methylome profiles of Populus deltoides cl.'55/65' and '10/17' parental lines and their intraspecific F1 hybrids lines was performed using methylated DNA immunoprecipitation (MeDIP) and high-throughput sequencing.
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Transcriptome sequencing of transgenic poplar (Populus × euramericana 'Guariento') expressing multiple resistance genes.
BMC Genet.
PUBLISHED: 06-20-2014
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Transgenic poplar (Populus × euramericana 'Guariento') plants harboring five exogenous, stress-related genes exhibit increased tolerance to multiple stresses including drought, salt, waterlogging, and insect feeding, but the complex mechanisms underlying stress tolerance in these plants have not been elucidated. Here, we analyzed the differences in the transcriptomes of the transgenic poplar line D5-20 and the non-transgenic line D5-0 using high-throughput transcriptome sequencing techniques and elucidated the functions of the differentially expressed genes using various functional annotation methods.
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Immunoglobulin G4-Related Hypertrophic Pachymeningitis with Skull Involvement.
Brain Tumor Res Treat
PUBLISHED: 06-12-2014
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Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, defined as focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease. Moreover, cases involving bone are even rarer. In this report, the authors describe a case of IgG4-related hypertrophic pachymeningitis involving the skull in a 65-year-old man presenting with generalized tonic seizures. There is a 2.4 cm diameter extra-axial mass at the vertex of the left frontal convexity and thickened dura mater with contrast enhancement on magnetic resonance (MR) imaging. In addition, the skull adjacent to the mass was focally enhanced. He underwent surgical resection of the enhanced mass and skull. Histopathological findings revealed chronic inflammation with fibrosis, and idiopathic hypertrophic intracranial pachymeningitis was considered. However, eight months after surgery, partial seizures developed and brain MR imaging revealed a recurrence adjacent to the previous mass. We decided to perform additional immunohistochemical staining of the previous specimen, instead of a re-excision. Immunohistochemical staining showed markedly increased IgG4 (+) plasma cells. Consequently, IgG4-related hypertrophic meningitis was confirmed. Since then, steroids and immunosuppressant medications were started. Follow-up MR imaging at 3 months after medication initiation demonstrated complete remission. In conclusion, IgG4-related hypertrophic pachymeningitis should be considered in the differential diagnosis of hypertrophic cranial pachymeningitis.
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Sex-related differences in the association between waist circumference and bone mineral density in a Korean population.
BMC Musculoskelet Disord
PUBLISHED: 05-11-2014
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Large waist circumference is linked to poor health. Investigations of the relationship between waist circumference, as an index of abdominal fat, and bone mineral density (BMD) have yielded inconsistent results. We investigated the association between abdominal obesity measured using waist circumference and BMD in a large-scale population-based study.
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The relationship between eosinophilia and bronchopulmonary dysplasia in premature infants at less than 34 weeks' gestation.
Korean J Pediatr
PUBLISHED: 04-30-2014
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Eosinophilia is common in premature infants, and its incidence increases with a shorter gestation period. We investigated the clinical significance of eosinophilia in premature infants born at <34 weeks gestation.
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Public Acceptance and Willingness to Hepatitis A Vaccination in Children Aged 7-18 Years in Republic of Korea.
J. Korean Med. Sci.
PUBLISHED: 04-18-2014
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Hepatitis A can cause serious illness among adolescents and adults with low vaccination coverage. Even though hepatitis A vaccine is one of the strong candidates for Korean national immunization program, adolescents aged older than 12 yr would not benefit. Our purpose was to assess the willingness and analyze the correlates of Korean mothers for hepatitis A (HepA) vaccination to develop strategies for HepA vaccination. A national telephone survey on 800 mothers with children aged 7-18 yr was conducted with random-digit dialing method. Sixty-two percent and 92% of the mothers reported that they were willing to HepA vaccination at current cost and at half of the current cost, respectively. However, at current cost, only 79% wished to vaccinate their child in an epidemic and 32% wished to vaccinate promptly. Having two or more children, not having future plans to send the child overseas, and low family income were significantly associated with not willing to HepA vaccination. Low perception of the susceptibility for hepatitis A and perception of the current cost as barrier increased the odds of unwillingness to vaccination at current cost and to prompt vaccination. The mothers' willingness to HepA vaccination for the children aged 7-18 yr in Korea was not very high at current cost and associated socioeconomic status and health-belief. Targeted intervention or strategies are needed to increase the HepA vaccination rate among children in Korea.
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New Reference Data on Bone Mineral Density and the Prevalence of Osteoporosis in Korean Adults Aged 50 Years or Older: The Korea National Health and Nutrition Examination Survey 2008-2010.
J. Korean Med. Sci.
PUBLISHED: 04-18-2014
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This cross-sectional study was performed to investigate the reference values for bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and the prevalence of osteoporosis in the Korean population by applying domestic reference data. In total, 25,043 Korean adults ?20 yr of age (11,792 men and 13,251 women) participated in the study. The BMDs of the total hip, femoral neck, and lumbar spine were measured by DXA (Discovery-W, Hologic Inc.), and subjects with a BMD - 2.5 standard deviations or lower than the mean BMD for young adults (20-29 yr old) were considered to have osteoporosis. When applying the new reference values determined in this study from Korean subjects, the overall prevalence of osteoporosis increased in men aged ?50 yr compared with that provided by the DXA manufacturer from Japanese subjects (12.2% vs. 7.8%, P<0.001) and decreased in postmenopausal women aged ?50 yr (32.9% vs. 38.7%, P<0.001). According to the findings of this study, use of the reference values provided by the DXA manufacturer has resulted in the underdiagnosis of osteoporosis in Korean men and the overdiagnosis of osteoporosis in Korean women. Our data will serve as valuable reference standards for the diagnosis and management for osteoporosis in the Korean population.
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Supratentorial Extraventricular Anaplastic Ependymoma Presenting with Repeated Intratumoral Hemorrhage.
Brain Tumor Res Treat
PUBLISHED: 04-15-2014
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Supratentorial extraventricular anaplastic ependymomas are extremely rare. We report the case of a 23-year-old male with a supratentorial extraventricular anaplastic ependymoma that presented with repeated intratumoral hemorrhage. The patient was diagnosed with an intracerebral hematoma in the left occipital lobe and underwent operation. The hematoma did not reveal tumor cells, but a new tumor grew in the same location 5 years later. Magnetic resonance imaging showed a tumor with intratumoral hemorrhage. The patient underwent the tumor resection. Intraoperative findings showed that the tumor had no continuity with the ventricle. Histopathological examinations confirmed an anaplastic ependymoma. The spinal evaluation was unremarkable, and radiotherapy was administered to the left occipital lobe. Four years later, the tumor recurred at the cervicomedullary junction and T8-T9 levels. This case demonstrates that anaplastic ependymomas should be included in the differential diagnoses of supratentorial extraventricular tumors presenting with repeated intratumoral hemorrhage.
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Quantitative determination and validation of avermectin B1a in commercial products using quantitative nuclear magnetic resonance spectroscopy.
Magn Reson Chem
PUBLISHED: 03-14-2014
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Nuclear magnetic resonance is defined as a quantitative spectroscopic tool that enables a precise determination of the number of substances in liquids as well as in solids. There is few report demonstrating the application of NMR in the quantification of avermectin B1a (AVB1a ); here, a proton nuclear magnetic resonance spectroscopy ((1) H NMR) using benzene [1-methoxy-4-(2-nitroethyl) (PMN)] as an internal standard and deuterochloroform as an NMR solvent was tested for the quantitative determination of AVB1a . The integrated signal of AVB1a at 5.56?ppm and the signal of PMN at 8.14?ppm in the (1) H NMR spectrum were used for quantification purposes. Parameters of specificity, linearity, accuracy, precision, intermediate precision, range, limit of detection (LOD), limit of quantification (LOQ), stability and robustness were validated. The established method was accurate and precise with good recovery (98.86%) and relative standard deviation (RSD) of assay (0.34%) within the linearity of the calibration curve ranging from 5.08 to 13.58?mg/ml (R(2) ?=?0.9999). The LOD and LOQ were 0.009 and 0.029?mg/ml, which indicated the excellent sensitivity of the method. The stability of the method was testified by a calculated RSD of 0.11%. The robustness was testified by modification of four different parameters, and the differences among each parameter were all less than 0.1%. Comparing with the assay described by the manufacturer of avermectin tablets, there was no significant difference between the assay obtained by HPLC and quantitative NMR (qNMR), which indicated qNMR was a simple and efficient method for the determination of AVB1a in commercial formulation products.
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Early aggressive nutrition enhances language development in very low-birthweight infants.
Pediatr Int
PUBLISHED: 03-06-2014
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Inadequate nutrition in very-low-birthweight (VLBW) infants is known to be associated with growth failure and poor neurological outcomes. We aimed to investigate the association of early aggressive protein and energy intakes with weight gain and 18-month neurodevelopmental outcomes in VLBW infants.
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Methylenetetrahydrofolate reductase 677 genotype-specific reference values for plasma homocysteine and serum folate concentrations in korean population aged 45 to 74 years: the Namwon study.
J. Korean Med. Sci.
PUBLISHED: 03-03-2014
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The reference interval for plasma total homocysteine (tHcy) and serum folate concentrations were estimated. Total of 3,154 reference individuals (1,029 men and 2,125 women) were selected based on stringent exclusion criteria. For plasma tHcy concentration (µM/L), reference values (median [5-95 percentile]) were 7.72 (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95 (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in the present study were lower than those in previous reports from other countries and Korea.
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Polymorphisms in DNA repair genes and MDR1 and the risk for non-Hodgkin lymphoma.
Int J Mol Sci
PUBLISHED: 03-03-2014
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The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (XRCC1 399 GA, OGG1 326 GG, BRCA1 871 TT, and WRN 787 TT) were associated with a decreased risk for NHL [odds ratio (OR)XRCC1 GA=0.80, p=0.02; OROGG1 GG=0.70, p=0.008; ORBRCA1 TT=0.71, p=0.048; ORWRN TT=0.68, p=0.01]. Conversely, the MGMT 115 CT genotype was associated with an increased risk for NHL (OR=1.25, p=0.04). In the MDR1 gene, the 1236 CC genotype was associated with a decreased risk for NHL (OR=0.74, p=0.04), and the 3435 CT and TT genotypes were associated with an increased risk (OR3435CT=1.50, p<0.0001; OR3435TT=1.43, p=0.02). These results suggest that polymorphisms in the DNA repair genes XRCC1, OGG1, BRCA1, WRN1, and MGMT and in the MDR1 gene may affect the risk for NHL in Korean patients.
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MDM2-MOF-H4K16ac axis contributes to tumorigenesis induced by Notch.
FEBS J.
PUBLISHED: 03-02-2014
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Identification of the epigenetic mechanisms involved in the transmission of Notch signaling is useful for personalized medicine. We observed that aberrantly high levels of Notch activity resulted in H4K16ac downregulation in hepatocellular carcinoma and breast cancer cell lines and tissues. This downregulated acetylation was a consequence of increased male on the first degradation following the upregulation of full-length murine double minute 2 in different cancer types. We observed that increases in male on the first could attenuate heterogeneity induced by aberrantly high levels of Notch activity. Our results provide new insights into the analysis and treatment of Notch-induced hepatocellular carcinoma and breast cancer.
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Impaired ? cell function in Chinese newly diagnosed type 2 diabetes mellitus with hyperlipidemia.
J Diabetes Res
PUBLISHED: 03-02-2014
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The objective is to explore the effects of hyperlipidemia on ? cell function in newly diagnosed type 2 diabetes mellitus (T2DM). 208 patients were enrolled in the study and were divided into newly diagnosed T2DM with hyperlipidemia (132 patients) and without hyperlipidemia (76 patients). Demographic data, glucose levels, insulin levels, lipid profiles, homeostasis model assessment for ? cell function index (HOMA-? ), homeostasis model assessment for insulin resistance index (HOMA-IR), and quantitative insulin-sensitivity check index (QUICKI) were compared between the two groups. We found that comparing with those of normal lipid levels, the subjects of newly diagnosed T2DM with hyperlipidemia were younger, and had declined HOMA-? . However, the levels of HOMA-? were comparable regardless of different lipid profiles (combined hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia). Multiple stepwise linear regression analysis showed that high fasting plasma glucose (FPG), decreased fasting insulin level (FINS), and high triglyceride (TG) were independent risk factors of ? cell dysfunction in newly diagnosed T2DM. Therefore, the management of dyslipidemia, together with glucose control, may be beneficial for T2DM with hyperlipidemia.
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Lack of association between serum gamma-glutamyltransferase and carotid atherosclerosis: The Namwon study.
Atherosclerosis
PUBLISHED: 02-28-2014
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Objectives: There is little evidence for an association between gamma-glutamyltransferase (GGT) and carotid atherosclerosis, an independent predictor of cardiovascular disease. We examined the association between serum GGT and carotid atherosclerotic parameters, including carotid intima-media thickness (IMT) and plaques, in a large general population. Methods: The study population consisted of community-dwelling adults who participated in the baseline survey of the Namwon Study. A total of 9120 subjects aged 45-74 years were included in the analyses. High-resolution B-mode ultrasound was used to measure carotid IMT and to evaluate the presence of carotid plaques. A mean carotid IMT of ?1.0 mm was classified as 'high carotid IMT'. Results: Serum GGT levels were classified into quartiles. In a fully adjusted model, we found no linear trend between GGT quartile and mean carotid IMT (P for trend = 0.167). Compared with the first quartile (the reference category), the odds ratios (ORs) and 95% confidence intervals (CIs) for high carotid IMT were 0.89 (0.68-1.16), 1.10 (0.84-1.43), and 0.97 (0.71-1.33) for the second, third, and fourth quartiles (P for trend = 0.754), respectively. The ORs (95% CIs) for carotid plaques were 0.89 (0.77-1.02), 0.95 (0.82-1.10), and 0.94 (0.79-1.11) for the second, third, and fourth quartiles, respectively, in the fully adjusted model (P for trend = 0.644). Conclusions: No significant association of GGT concentration with carotid IMT or plaques was found in this large cross-sectional study. Further longitudinal studies are needed to confirm our findings.
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Gender Differences in the Association between Depressive Symptoms and Carotid Atherosclerosis among Middle-Aged and Older Koreans: The Namwon Study.
J. Korean Med. Sci.
PUBLISHED: 02-27-2014
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We investigated the association of depressive symptoms with carotid intima-media thickness (IMT) and plaques in the general Korean population. A total of 7,554 Korean males and females aged 45-74 yr who were free from cardiovascular diseases were included in the analyses. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). Subjects with a score of ?16 were classified as having clinically significant depressive symptoms. Carotid ultrasonography was used to measure mean carotid IMT (C-IMT) and to determine the presence of plaques. A significant association between depressive symptoms and C-IMT was observed only in females. After adjustment for established cardiovascular risk factors, females with depressive symptoms had significantly greater C-IMT than females without depressive symptoms (mean difference 0.011±0.004 mm; 95% confidence interval, 0.003-0.019 mm). Compared with controls, the fully adjusted risk of females with depressive symptoms for abnormal C-IMT (?1.0 mm) was significant (odds ratio, 1.63; 95% confidence interval, 1.16-2.30). No significant association between depressive symptoms and carotid plaques was observed in either gender. This study shows a significant association between depressive symptoms and C-IMT in middle-aged and older females.
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Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells.
Sci Rep
PUBLISHED: 02-06-2014
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PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.
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Normative and mean carotid intima-media thickness values according to metabolic syndrome in Koreans: the Namwon study.
Atherosclerosis
PUBLISHED: 02-05-2014
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We determined the gender- and age-specific normative values of carotid intima-media thickness (IMT) in a healthy Korean population. We also present the mean age-specific carotid IMT values according to the presence of metabolic syndrome (MetS) and the number of MetS components.
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Microarrays formed by microfluidic spinning as multidimensional microreactors.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-30-2014
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The exploration of methods allowing chemical reactions to be carried out at ultrasmall scales is of great scientific and technological interest. We report herein a microfluidic spinning technique for the fabrication of softened-polymer microarrays for use as multidimensional microreactors and the application of these microreactors in the synthesis of fluorescent nanocrystals. Highly aligned microarrays and controlled-angle grids were readily constructed from microfluidically spun polyvinylpyrrolidone (PVP) microfibers. One-zero dimensional (1D-0D), one-one dimensional (1D-1D), and one-two dimensional (1D-2D) microreactors were then produced by the intersections between microfibers and droplets, crossed microfibers, and microfibers and a PVP film, respectively; each component can be doped with different reagents. Specific examples show that these multidimensional microreactors enable the in situ generation of fluorescent nanocrystals without ligands within minutes.
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Synthesis and characterization of glycoconjugated porphyrin triphenylamine hybrids for targeted two-photon photodynamic therapy.
J. Org. Chem.
PUBLISHED: 01-29-2014
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In order to avoid side effects at the time of cancer eradication to the patients, the selectivity of treatments has become of strategic importance. In the case of photodynamic therapy (PDT), two-photon absorption combined with active targeting of tumors could allow both spatial and chemical selectivity. In this context, we present the synthesis, spectroscopic, and biological properties of a series of porphyrin-triphenylamine hybrids with excellent singlet oxygen production capacities and good two-photon absorption.
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Induced multipotency in adult keratinocytes through down-regulation of ?Np63 or DGCR8.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-21-2014
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The roles of microRNAs (miRNAs) and the miRNA processing machinery in the regulation of stem cell biology are not well understood. Here, we show that the p53 family member and p63 isoform, ?Np63, is a transcriptional activator of a cofactor critical for miRNA processing (DGCR8). This regulation gives rise to a unique miRNA signature resulting in reprogramming cells to multipotency. Strikingly, ?Np63(-/-) epidermal cells display profound defects in terminal differentiation and express a subset of markers and miRNAs present in embryonic stem cells and fibroblasts induced to pluripotency using Yamanaka factors. Moreover, ?Np63(-/-) epidermal cells transduced with an inducible DGCR8 plasmid can differentiate into multiple cell fates in vitro and in vivo. We found that human primary keratinocytes depleted of ?Np63 or DGCR8 can be reprogrammed in 6 d and express a unique miRNA and gene expression signature that is similar but not identical to human induced pluripotent stem cells. Our data reveal a role for ?Np63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells.
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High prevalence of vitamin D deficiency in adults aged 50 years and older in Gwangju, Korea: the Dong-gu Study.
J. Korean Med. Sci.
PUBLISHED: 01-17-2014
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Vitamin D plays an important role in bone metabolism and maintaining bone health. Recently, new evidence has revealed that vitamin D affects chronic diseases such as autoimmune diseases, cardiovascular diseases and certain cancers. The aim of this study was to evaluate the vitamin D status and the prevalence of vitamin D deficiency in an urban Korean population. This study included 8,976 participants (3,587 men and 5,389 women) aged 50 yr and older. Serum 25(OH)D level was measured by chemiluminescent microparticle immunoassay. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] was 59.7% and 86.5% in men and women, respectively. The prevalence of vitamin D deficiency increased significantly with age in men, but not in women and it decreased from April to July, more prominently in men than in women. These results suggest that sun exposure, intake of vitamin D supplement, and regular physical activities is recommended in an urban Koreans, especially in women.
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Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming.
Cell Stem Cell
PUBLISHED: 01-14-2014
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Obtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2(-/-)/?c(-/-) mice and secrete more than 300 ?g/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications.
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APOE polymorphism and carotid atherosclerosis in Korean population: the Dong-gu Study and the Namwon Study.
Atherosclerosis
PUBLISHED: 01-10-2014
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We evaluated the association between APOE polymorphism and carotid atherosclerosis in two large independent cohorts from South Korea.
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The incidence of acute myocardial infarction in relation to overweight and obesity: a meta-analysis.
Arch Med Sci
PUBLISHED: 01-05-2014
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Epidemiological evidence suggests that overweight and obesity have been associated with acute myocardial infarction (AMI). However, data on this issue are controversial. This study aims to use meta-analysis to determine whether overweight and obesity are related to AMI.
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Human RAD6 Promotes G1-S Transition and Cell Proliferation through Upregulation of Cyclin D1 Expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.
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CXCR6 deficiency attenuates pressure overload-induced monocytes migration and cardiac fibrosis through downregulating TNF-?-dependent MMP9 pathway.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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An immerging role of TNF-? in collagen synthesis and cardiac fibrosis implies the significance of TNF-? production in the development of myocardial remodeling. Our previous study showed a reduction of TNF-? and attenuated cardiac remodeling in CXCR6 knockout (KO) mice after ischemia/reperfusion injury. However, the potential mechanism of TNF-?-mediated cardiac fibrosis with pressure overload has not been well elucidated. In the present study, we aim to investigate the role of CXCR6 in TNF-? release and myocardial remodeling in response to pressure overload. Pressure overload was performed by constriction of transverse aorta (TAC) surgery on CXCR6 KO mice and C57 wild-type (WT) counterparts. At 6 weeks after TAC, cardiac remodeling was assessed by echocardiography, cardiac TNF-? release and its type I receptor (TNFRI), were detected by ELISA and western blot, collagen genes Col1a1 (type I) and Col3a1 (type III) were examined by real-time PCR. Compared with CXCR6 WT mice, CXCR6 KO mice exhibited less cardiac dysfunction, reduced expression of TNFRI, Col1a1 and Col3a. In vitro, we confirmed that CXCR6 deficiency led to reduced homing and infiltration of CD11b(+) monocytes, which contributed to attenuated TNF-? release in myocardium. Furthermore, TNFRI antagonist pretreatment blocked AT1 receptor signaling and NOX4 expression, reduced collagen synthesis, and blunted the activity of MMP9 in CXCR6 WT mice after TAC, but these were not observed in CXCR6 KO mice. In the present work, we propose a mechanism that CXCR6 is essential for pressure overload-mediated myocardial recruitment of monocytes, which contributes to cardiac fibrosis through TNF-?-dependent MMP9 activation and collagen synthesis.
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Expression and molecular evolution of two DREB1 genes in black poplar (Populus nigra).
PLoS ONE
PUBLISHED: 01-01-2014
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Environmental stresses such as low temperature, drought, and high salinity significantly affect plant growth and yield. As selective forces, these adverse factors play essential roles in shaping phenotypic variation in plant populations. Black poplar (Populus nigra) is an economically and ecologically important forest tree species with widely distributed populations and is thus suitable for experiments detecting evolutionary footprints left by stress. Here, we performed expression and evolutionary analysis of two duplicated DREB A1-subgroup (DREB1) genes, PnDREB68 and PnDREB69, encoding transcription factors that are involved in stress responses. The two genes showed partially overlapping but distinct expression patterns in response to stresses. These genes were strongly and rapidly induced by cold stress in leaves, stems, and roots. In leaf tissue, dehydration stress induced the expression of PnDREB68 but not PnDREB69. PnDREB69 displayed more rapid responses and longer expression durations than PnDREB68 under salt and ABA stress, respectively. Based on single nucleotide polymorphism (SNP) analysis, we found significant population genetic differentiation, with a greater FST value (0.09189) for PnDREB69 than for PnDREB68 (0.07743). Nucleotide diversity analysis revealed a two-fold higher ?T for PnDREB68 than for PnDREB69 (0.00563 vs. 0.00243), reflecting strong purifying selection acting on the former. The results suggest that positive selection acted on PnDREB69, as evidenced by neutral testing using Tajima's D statistic. The distinct selective forces to which each of the genes was subjected may be associated with expression divergence. Linkage disequilibrium (LD) was low for the sequenced region, with a higher level for PnDREB68 than for PnDREB69. Additionally, analysis of the relationship among carbon isotope ratios, SNP classes and gene expression, together with motif and domain analysis, suggested that 14 polymorphisms within the two genes may be candidates for an association study of important traits such as water use efficiency/drought tolerance in black poplar.
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Generation of mastitis resistance in cows by targeting human lysozyme gene to ?-casein locus using zinc-finger nucleases.
Proc. Biol. Sci.
PUBLISHED: 01-01-2014
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Mastitis costs the dairy industry billions of dollars annually and is the most consequential disease of dairy cattle. Transgenic cows secreting an antimicrobial peptide demonstrated resistance to mastitis. The combination of somatic cell gene targeting and nuclear transfer provides a powerful method to produce transgenic animals. Recent studies found that a precisely placed double-strand break induced by engineered zinc-finger nucleases (ZFNs) stimulated the integration of exogenous DNA stretches into a pre-determined genomic location, resulting in high-efficiency site-specific gene addition. Here, we used ZFNs to target human lysozyme (hLYZ) gene to bovine ?-casein locus, resulting in hLYZ knock-in of approximately 1% of ZFN-treated bovine fetal fibroblasts (BFFs). Gene-targeted fibroblast cell clones were screened by junction PCR amplification and Southern blot analysis. Gene-targeted BFFs were used in somatic cell nuclear transfer. In vitro assays demonstrated that the milk secreted by transgenic cows had the ability to kill Staphylococcus aureus. We report the production of cloned cows carrying human lysozyme gene knock-in ?-casein locus using ZFNs. Our findings open a unique avenue for the creation of transgenic cows from genetic engineering by providing a viable tool for enhancing resistance to disease and improving the health and welfare of livestock.
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The application of quantitative NMR for the facile, rapid and reliable determination of clindamycin phosphate in a conventional tablet formulation.
Magn Reson Chem
PUBLISHED: 01-01-2014
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Spectroscopic tools such as NMR can be applied to the quantitative analysis of active pharmaceutical ingredients with relative ease and accuracy. Here, we demonstrate the quantification of clindamycin phosphate (CLP) in a conventional tablet formulation, performed using potassium hydrogen phthalate (KHP) as the internal standard and deuterium oxide (D2O) as the NMR solvent. The methyl protons signal of CLP at 0.72 ppm (triplet) relative to the signal of KHP at 7.37-7.40 ppm (multiplet) was used for quantification purposes using (1)H NMR. This method was shown to be specific and linear (r = 0.9997) within the CLP concentration range from 7.2 to 23.1 mg per 0.5 ml of D2O. The maximum relative standard deviation (RSD) of accuracy and precision was calculated at 0.39% and 0.64%, respectively. The limits of detection (LOD) and quantification were 0.04 and 0.11 mg/ml, respectively. The method was highly stable with a calculated RSD of 0.03%. The robustness of the method was demonstrated by changing four different parameters, and the difference among each parameter was ? 0.78%. The findings of this work were in good agreement with previously reported conventional HPLC-based approaches, highlighting its applicability in the determination of other active pharmaceutical ingredients in conventional formulations for quality control purposes.
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Dose-Response Relationship Between Serum ?-Glutamyltransferase and Arterial Stiffness in Korean Adults: The Namwon Study.
J Epidemiol
PUBLISHED: 10-26-2013
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Background: The results of epidemiologic studies of the association between serum ?-glutamyltransferase (GGT) and brachial-ankle pulse wave velocity (baPWV) have been inconsistent. We examined the association between serum GGT and arterial stiffness in a general population of Korean adults.Methods: The study population consisted of 6314 community-dwelling Koreans who participated in the baseline survey of the Namwon Study. We analyzed sex-specific association between serum GGT and arterial stiffness, as measured by baPWV.Results: There was a significant progressive increase in age-adjusted mean baPWV across quartiles of GGT in both sexes. In fully adjusted analysis, as compared with the lowest quartile, the odds ratios (95% CI) for high baPWV (ie, sex-specific fifth quintile) were 1.51 (1.03-2.23), 1.82 (1.22-2.72), and 2.80 (1.79-4.40) among men (P-trend <0.001), and 1.11 (0.81-1.52), 1.29 (0.94-1.76), and 1.47 (1.04-2.08) among women (P-trend <0.001), for the second, third, and fourth quartiles of GGT, respectively.Conclusions: This population-based study examined the dose-response relationship between GGT and arterial stiffness as measured by baPWV in both sexes. The association between GGT and arterial stiffness was stronger among men. Additional longitudinal studies are needed to examine the relationship between GGT and arterial stiffness and clarify the mechanism underlying the association.
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Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid.
J. Lipid Res.
PUBLISHED: 10-01-2013
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We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDL receptor-null (LDLR?/?) mice fed a Western diet (WD). Here we demonstrate that WD increases unsaturated (but not saturated) LPA levels in the small intestine of LDLR?/? mice and causes changes in small intestine gene expression. Confirmation of microarray analysis by quantitative RT-PCR showed that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F) to WD prevented many WD-mediated small intestine changes in gene expression. If instead of feeding WD, unsaturated LPA was added to chow and fed to the mice: i) levels of LPA in the small intestine were similar to those induced by feeding WD; ii) gene expression changes in the small intestine mimicked WD-mediated changes; and iii) changes in plasma serum amyloid A, total cholesterol, triglycerides, HDL-cholesterol levels, and the fast-performance liquid chromatography lipoprotein profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to LPA-supplemented chow prevented the LPA-induced changes. We conclude that: i) WD-mediated systemic inflammation and dyslipidemia may be in part due to WD-induced increases in small intestine LPA levels; and ii) Tg6F reduces WD-mediated systemic inflammation and dyslipidemia by preventing WD-induced increases in LPA levels in the small intestine.
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Molecular cloning and functional analysis of the Populus deltoides remorin gene PdREM.
Tree Physiol.
PUBLISHED: 09-26-2013
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Remorins play vital roles in signal transduction, energy transformation, ion flow and transport in plants. Upregulation of remorins correlates with dehiscence and cell maturation; however, no studies have been performed to elucidate the function of remorins in tree species. In this study, a Populus deltoides (Marsh.) plasma membrane-binding protein remorin gene (PdREM) was cloned and characterized by investigating its expression pattern and creating transgenic hybrid poplar (P. davidiana Dode × P. bolleana Lauche) lines expressing sense or antisense PdREM. PdREM was specifically expressed in leaf buds, and immature and mature phloem in P. deltoides. Downregulation of PdREM increased plant height, stem diameter, number of leaves, size of the xylem and phloem zones and induced expression of cell wall biosynthesis- and microfibril angle (MFA)-related genes. Overexpression of PdREM retarded vegetative growth. PdREM may negatively regulate vascular growth by inhibiting secondary cell wall expansion in poplar. In addition, antisense PdREM transgenic poplar had a lower MFA, suggesting that PdREM might contribute to sheet strength and wood properties in poplar. This study sheds light on the molecular mechanism of PdREM in P. deltoides growth and development, and lays the foundation for future functional genomics research into wood formation and the genetic engineering of forest trees with improved wood quality traits.
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Regulation of trehalase expression inhibits apoptosis in diapause cysts of Artemia.
Biochem. J.
PUBLISHED: 09-26-2013
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Trehalase, which specifically hydrolyses trehalose into glucose, plays an important role in the metabolism of trehalose. Large amounts of trehalose are stored in the diapause encysted embryos (cysts) of Artemia, which are not only vital to their extraordinary stress resistance, but also provide a source of energy for development after diapause is terminated. In the present study, a mechanism for the transcriptional regulation of trehalase was described in Artemia parthenogenetica. A trehalase-associated protein (ArTAP) was identified in Artemia-producing diapause cysts. ArTAP was found to be expressed only in diapause-destined embryos. Further analyses revealed that ArTAP can bind to a specific intronic segment of a trehalase gene. Knockdown of ArTAP by RNAi resulted in the release of cysts with coarse shells in which two chitin-binding proteins were missing. Western blotting showed that the level of trehalase was increased and apoptosis was induced in these ArTAP-knockdown cysts compared with controls. Taken together, these results show that ArTAP is a key regulator of trehalase expression which, in turn, plays an important role in trehalose metabolism during the formation of diapause cysts.
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Common genetic variants at 1q22 and 10q23 and gastric cancer susceptibility in a Korean population.
Tumour Biol.
PUBLISHED: 09-16-2013
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Genetic variants at 1q22 and 10q23 were identified as genetic markers of both gastric cancer and esophageal squamous cell carcinoma susceptibility by two genome-wide association studies. The aim of this study was to determine whether rs4072037A?>?G in MUC1 at 1q22 and rs2274223A?>?G in PLCE1 at 10q23 are associated with a risk of gastric cancer in a Korean population. We conducted a large-scale case-control study of 3,245 patients with gastric cancer and 1,700 controls. The allele frequencies of rs4072037G and rs2274223G were 11.2 and 25.5 % among patients with gastric cancer, compared with 12.8 and 26.4 %, respectively, among controls. We found that the rs4072037 AG genotype was significantly associated with a reduced risk of gastric cancer [odds ratios (OR)?=?0.78; 95 % confidence interval (CI)?=?0.67-0.91 for AG vs AA]. Compared with the rs2274223 AA genotype, we found a significant association between the rs2274223 AG genotype and a weakly reduced risk of gastric cancer (OR?=?0.87; 95 % CI?=?0.76-0.99 for AG vs AA). Our data suggest that genetic variants at 1q22 and 10q23 play a role in gastric carcinogenesis.
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[Briefing on the 61st academic conference of Japanese Acupuncture Association].
Zhongguo Zhen Jiu
PUBLISHED: 08-24-2013
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The main content of the 61st Academic Conference of Japanese Acupuncture Association is introduced and summarized in this article. Different from former conferences, it focuses on the academic activity which take patient into the major consideration, and on the feasibility study of aerospace acupuncture treatment. Meanwhile, study on Japanese technique of shallow insertion with fine needle and its results are also introduced. The developing tendency of Japanese Acupuncture Association is discussed at the meeting as well.
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Effect of urinary bisphenol a on androgenic hormones and insulin resistance in preadolescent girls: a pilot study from the Ewha birth & growth cohort.
Int J Environ Res Public Health
PUBLISHED: 08-06-2013
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To assess the effect of urinary bisphenol A (BPA) on repeated measurements of androgenic hormones and metabolic indices, we used multivariate analysis of variance (MANOVA) adjusted for potential confounders at baseline. During July to August 2011, 80 preadolescent girls enrolled in the Ewha Birth & Growth Cohort study participated in a follow-up study and then forty-eight of them (60.0%) came back one year later. Baseline levels of estradiol and androstenedione were higher in the BPA group than in the non-BPA group. One year later, girls in the high BPA exposure group showed higher levels of androstenedione, testosterone, estradiol, and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index, than those in the other groups (p < 0.05). In MANOVA, estradiol and androstenedione showed significant differences among groups, while dehydroepiandrosterone, insulin, and HOMA-IR showed marginally significant differences. Exposure to BPA may affect endocrine metabolism in preadolescents. However, further investigation is required to elucidate the mechanisms linking BPA with regulation of androgenic hormones.
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Synthesis of a liquid-crystalline resin monomer with the property of low shrinkage polymerization.
Dent Mater J
PUBLISHED: 08-02-2013
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To reduce the polymerization shrinkage of the dental resin composites, a new liquid-crystalline resin monomer was developed. The acrylate liquid crystalline resin monomer (ALCRM), (4-3-(acryloyloxy)-2-hydroxypropoxy) phenyl 4-(3-(acryloyloxy)-2-hydroxypropoxy) benzoate, was synthesized by a three-step method. Using the ALCRM as the main monomer, the degree of conversion (DC) and the volume shrinkage of the resin matrix were compared with the traditional composite resin monomer (Bis-GMA), 2,2-bis[4-(2-hydroxy-3-methacryloyloxy-propoxy)-phenyl] propane. The new monomer showed liquid crystalline characteristics with a mesomorphic phasetransition temperature between 18ºC and 42ºC. When copolymerized with triethylene glycol dimethacrylate (TEGDMA) at a weight ratio of 7:3, the DC of ALCRM was higher and the volume shrinkage was 3.62±0.26%, which was less than that of the Bis-GMA. The ALCRM exhibits promising potential for the development of superior dental resins with low volume shrinkage.
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Thyroid cancer is the most common cancer in women, based on the data from population-based cancer registries, South Korea.
Jpn. J. Clin. Oncol.
PUBLISHED: 07-25-2013
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Similar to worldwide trends, the incidence of thyroid cancer in South Korea has increased steadily in recent decades. We examined the trends in thyroid cancer incidence in Gwangju and Jeonnam provinces between 1996 and 2010, and identified 19 881 cases (men 3282/16.5%; women 16 599/83.5%) from the Gwangju Cancer Registry and Jeonnam Cancer Registry databases, which are population-based cancer registries. Age-standardized incidence rates per 100 000 persons, using hypothetical world standard population (Segi), increased from 1.9 in 1996 to 27.0 in 2010 in men, and from 10.6 to 111.3 in women, respectively. The estimated annual percentage changes (95% confidence interval) of age-standardized incidence rates were 27.1% (24.6-29.6) and 19.7% (16.4-23.2) for men and women, respectively, during the same period. The proportion of papillary-type thyroid cancer increased from 74.2 and 75.4% in 1996 to 97.9 and 98.3% in 2010 for men and women, respectively. We found the most prominent increasing trends and the highest incidence rate of thyroid cancer among those that have ever been reported. Thyroid cancer has been the leading cancer in women since 2003 and is now the fifth most common cancer in men in Gwangju and Jeonnam, South Korea.
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Isolation and characterization of mesenchymal stem cells derived from fetal bovine liver.
Cell Tissue Bank
PUBLISHED: 07-19-2013
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Bovine liver-derived mesenchymal stem cells (bLMSCs) were isolated from the liver tissue of 4-6 months old fetal calf, and then characterized by immunofluorescence and RT-PCR. We found that primary bLMSCs could be subcultured to 44 passages, the total culture time in vitro was 192 days. The results of surface antigen detection showed that bBMSCs expressed CD29, CD44, CD73, CD90, CD106 and CD166 but not expressed endothelial cells and hematopoietic cells specific marker CD34, CD45 and BLA-DR. The results of growth kinetics, colony-forming cell assay and cell cycle analysis indicated that the fetal bovine LMSCs had good proliferation ability in vitro. The cells from passages 7 were successfully induced to differentiate into osteoblasts, adipocytes and chondrocytes. The results indicate the potential for multi-lineage differentiation of bLMSCs that may represent an ideal candidate for cellular transplantation therapy.
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The effect of an APOE polymorphism on cognitive function depends on age.
J. Neurol.
PUBLISHED: 07-19-2013
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It remains controversial whether APOE E4 polymorphism is related to cognitive function in general population. We aimed to evaluate an association between the APOE E4 genotype and cognitive function, and whether this association may differ by age. Cognitive function was assessed using the Korean version of modified Mini-Mental State Examination (K-mMMSE) in 10,371 Koreans aged 45-74 years in Namwon City. According to the APOE E4 status, all participants were classified as non-carriers, heterozygotes, or homozygotes. Multiple linear and logistic regression models were used to evaluate the association between APOE genotypes and cognition. The frequency of APOE genotypes in the study population was 0.4, 10.1, 1.1, 72.9, 14.7 and 0.8 % for E2E2, E2E3, E2E4, E3E3, E3E4, and E4E4, respectively. Compared to the APOE E4 non-carriers, the heterozygotes and homozygotes showed 1.3 and 7.3 % lower K-mMMSE scores at 65-74 years and 0.8 and 4.6 % higher scores at 45-55 years, respectively. Educational attainment modified the effect of APOE E4 on cognitive function in the 45-54 age group (p for interaction =0.003), showing that the E4 carriers with no-formal education showed significantly higher cognitive function than those with formal education. The present study demonstrates that the effect of APOE E4 on cognitive function depends on age and education.
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[Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate cancer cells].
Zhonghua Nan Ke Xue
PUBLISHED: 07-19-2013
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To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism.
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Mendelian randomization analysis of the effect of maternal homocysteine during pregnancy, as represented by maternal MTHFR C677T genotype, on birth weight.
J Epidemiol
PUBLISHED: 07-13-2013
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We used Mendelian randomization analysis to investigate the causal relationship between maternal homocysteine level, as represented by maternal methylenetetrahydrofolate reductase (MTHFR) C677T genotype, with the birth weight of offspring.
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Interfacial fabrication of single-crystalline ZnTe nanorods with high blue fluorescence.
J. Am. Chem. Soc.
PUBLISHED: 07-11-2013
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From the perspective of practical application, the development of fluorescent nanocrystals with low toxicity and desirable optical properties is highly needed. Here we report a new liquid-liquid interfacial synthesis of single-crystalline ZnTe nanorods with high fluorescence. With the use of long-alkyl-chain fatty acid as the capping ligand, the reaction of zinc acrylate with NaHTe under a moderate temperature (~90 °C) at the toluene/water interface yielded high-quality ZnTe nanorods. The preparation parameters and the growth mechanism were thoroughly investigated. The as-prepared ZnTe nanorods exhibited stable blue fluorescence with quantum yield up to 60%. This bright and stable emission gives promise for the use of these relatively benign nanorods in various applications such as blue light-emitting diodes.
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The association of ankle brachial index with left ventricular hypertrophy and left ventricular mass index: the Dong-gu study.
VASA
PUBLISHED: 07-05-2013
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To investigate the association between ankle-brachial index (ABI), left ventricular hypertrophy (LVH) and left ventricular mass index (LVMI) in a general population.
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Robust self-healing hydrogels assisted by cross-linked nanofiber networks.
Sci Rep
PUBLISHED: 05-30-2013
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Given increasing environmental and energy issues, mimicking nature to confer synthetic materials with self-healing property to expand their lifespan is highly desirable. Just like human skin recovers itself upon damage with the aid of nutrient-laden blood vascularization, designing smart materials with microvascular network to accelerate self-healing is workable but continues to be a challenge. Here we report a new strategy to prepare robust self-healing hydrogels assisted by a healing layer composed of electrospun cross-linked nanofiber networks containing redox agents. The hydrogels process high healing rate ranging from seconds to days and great mechanical strengths with storage modulus up to 0.1 MPa. More interestingly, when the healing layer is embedded into the crack of the hydrogel, accelerated self-healing is observed and the healing efficiency is about 80%. The healing layer encourages molecular diffusion as well as further cross-linking in the crack region of the hydrogel, responsible for enhanced healing efficiency.
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Lipopolysaccharide neutralization by a novel peptide derived from phosvitin.
Int. J. Biochem. Cell Biol.
PUBLISHED: 05-29-2013
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Lipopolysaccharide (LPS), also known as endotoxin, is the primary trigger of sepsis, which is associated with high mortality in patients. No therapeutic agents are currently efficacious enough to protect patients from sepsis characterized by LPS-mediated tissue damage and organ failure. Previously, a phosvitin-derived peptide, Pt5, which consists of the C-terminal 55 residues of zebrafish phosvitin, has been shown to function as an antibacterial agent. In this study, we have generated six mutants by site-directed mutagenesis based on the sequence of Pt5, and found that one of the six mutants, Pt5e, showed the strongest bactericidal activities against Escherichia coli and Staphylococcus aureus. We then demonstrated that Pt5e was able to bind to LPS and lipoteichoic acid (LTA). More importantly, we showed that Pt5e significantly inhibited LPS-induced tumor-necrosis factor (TNF)-? and interleukin (IL)-1? release from murine RAW264.7 cells and considerably reduced serum TNF-? and IL-1? levels in mice. Additionally, Pt5e protected the liver from damage by LPS, and remarkably promoted the survival rate of the endotoxemia mice. Furthermore, Pt5e displayed no cytotoxicity to murine RAW264.7 macrophages and no hemolytic activity toward human red blood cells. These data together indicate that Pt5e is an endotoxin-neutralizing agent with a therapeutic potential in clinical treatment of LPS-induced sepsis.
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Genetic variations in the PRKAA1 and ZBTB20 genes and gastric cancer susceptibility in a Korean population.
Mol. Carcinog.
PUBLISHED: 05-29-2013
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A recent genome-wide association study (GWAS) identified new susceptibility single-nucleotide polymorphisms (SNPs) rs13361707 (PRKAA1 and PTGER4 gene on 5p13.1) and rs9841504 (ZBTB20 gene on 3q13.31) that were significantly associated with non-cardia gastric cancer. The aim of this study was to determine whether rs13361707 and rs9841504 polymorphisms are associated with the risk of gastric cancer in a Korean population. We conducted a large-scale case-control study of 3245 gastric cancer patients and 1700 controls. The allele frequencies for rs13361707 C and rs9841504 G were 53.5% and 18.3% among gastric cancer cases, compared with 47.1% and 17.2% among controls, respectively. We found that rs13361707 TC and CC genotypes were associated with increased risk for gastric cancer (odds ratios [OR] = 1.29; 95% confidence interval [CI] = 1.11-1.51 for TC vs. TT and 1.68; 1.41-2.01 for CC vs. TT). However, we found no significant association between rs9841504 and gastric cancer risk (OR = 1.11; 0.97-1.28 for CG vs. CC; OR = 1.09; 0.77-1.53 for GG vs. CC). We observed no significant interactions between rs13361707 and rs9841504 polymorphisms and age, gender, smoking habit, alcohol consumption, and clinicopathologic characteristics such as anatomical tumor location and histological type. Our study showed that the rs13361707 polymorphism was associated with increased risk of gastric cancer in a Korean population. This finding provides further evidence that genetic variant of PRKAA1 and PTGER4 genes may contribute to the gastric carcinogenesis. However, we found no association between rs9841504 and gastric cancer risk.
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Plasma cell enrichment enhances detection of high-risk cytogenomic abnormalities by fluorescence in situ hybridization and improves risk stratification of patients with plasma cell neoplasms.
Arch. Pathol. Lab. Med.
PUBLISHED: 05-01-2013
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Methods for plasma cell enrichment of bone marrow (BM) specimens can increase the sensitivity of fluorescence in situ hybridization (FISH) for detecting cytogenomic abnormalities. There are no published reports using these methods to evaluate high-risk cytogenomic abnormalities in patients with plasma cell neoplasms (PCNs) after therapy.
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Label-free quantitative proteomics analysis of dormant terminal buds of poplar.
Mol. Biol. Rep.
PUBLISHED: 04-29-2013
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Induction and break of bud dormancy are important features for perennial plants surviving extreme seasonal variations in climate. However, the molecular mechanism of the dormancy regulation, still remain poorly understood. To better understand the molecular basis of poplar bud dormancy, we used a label-free quantitative proteomics method based on nanoscale ultra performance liquid chromatography-ESI-MS(E) for investigation of differential protein expression during dormancy induction, dormancy, and dormancy break in apical buds of poplar (Populus simonii × P. nigra). Among these identified over 300 proteins during poplar bud dormancy, there are 74 significantly altered proteins, most of which involved in carbohydrate metabolism (22 %), redox regulation (19 %), amino acid transport and metabolism (10 %), and stress response (8 %). Thirty-one of these proteins were up-regulated, five were down-regulated during three phase, and thirty-eight were expressed specifically under different conditions. Pathway analysis suggests that there are still the presence of various physiological activities and a particular influence on photosynthesis and energy metabolism during poplar bud dormancy. Differential expression patterns were identified for key enzymes involved in major metabolic pathways such as glycolysis and the pentose phosphate pathway, thus manifesting the interplay of intricate molecular events in energy generation for new protein synthesis in the dormant buds. Furthermore, there are significant changes present in redox regulation and defense response proteins, for instance in peroxidase and ascorbate peroxidase. Overall, this study provides a better understanding of the possible regulation mechanisms during poplar bud dormancy.
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I?B kinase ? (IKK?) inhibits p63 isoform ? (TAp63?) transcriptional activity.
J. Biol. Chem.
PUBLISHED: 04-15-2013
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Previously, we reported that I?B kinase-?(IKK?) phosphorylates and stabilizes TAp63?. However, the effect of this phosphorylation on TAp63? transcriptional activity remains unclear. In this study, we showed that overexpression of IKK?, but not its kinase dead mutant and IKK?, can surprisingly inhibit TAp63? transcriptional activity as measured by luciferase assays and real-time PCR analyses of p63 target genes. This inhibition was impaired by ACHP, an IKK? inhibitor, and enhanced by TNF? that activates IKK?. Consistently, IKK? inhibited the binding between TAp63? and p300, a co-activator of TAp63?, and consequently counteracted the positive effect of p300 on TAp63? transcriptional activity. Through phosphorylation site prediction and mass spectrometry, we identified that Ser-4 and Ser-12 of p63 are IKK?-targeting residues. As expected, IKK? fails to suppress the transcriptional activity of the S4A/S12A double mutant p63. These results indicate that IKK? can suppress TAp63? activity by interfering with the interaction between TAp63? and p300.
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Association of adiponectin gene polymorphism with birth weight in Korean neonates.
Twin Res Hum Genet
PUBLISHED: 04-03-2013
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Adiponectin has been associated with insulin resistance and type 2 diabetes mellitus and possibly fetal growth. Our aim was to assess the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and the birth sizes. We investigated four SNPs of ADIPOQ (rs182052, rs2241766, rs1501299, and rs266729) and birth height and weight in 237 healthy full-term neonates. The neonates with the rs182052 G allele had a greater birth weight (p = .043 in the dominant model) and a higher ponderal index (p = .028 in the additive model). The rs2241766 G allele was associated with a greater birth weight (p = .016 in the recessive model). In a logistic regression analysis, the homozygotes for the rs182052 G allele and those for the rs2241766 G allele showed a significant association with a greater birth weight above 90 percentile (OR 2.75, 95% CI 1.13-6.70 and OR 5.15, 95% CI 1.66-15.99, respectively). In conclusion, we found an association between rs182052 and rs2241766 and birth weight and ponderal index among healthy neonates and suggested that adiponectin might have some roles in fetal growth.
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Synthesis and structure-activity relationship of 8-substituted protoberberine derivatives as a novel class of antitubercular agents.
Chem Cent J
PUBLISHED: 04-01-2013
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The emergence of multi-drug resistant tuberculosis (MDR-TB) has heightened the need for new chemical classes and innovative strategies to tackle TB infections. It is urgent to discover new classes of molecules without cross-resistance with currently used antimycobacterial drugs.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.